The present invention relates to systems and methods for early detection of body malfunctions in a patient based on real time monitoring of urinary parameters or urine from a catheterized patent, indicative of changes of state in the human body.
The kidney is an organ which performs several functions in a mammalian body. It receives approximately 20% of the blood flow from cardiac output. The kidney acts as a filter and normally excretes metabolic and foreign waste products in urine at a rate proportional to the blood flow received from the heart. The excretory function serves, inter alia, to maintain fluid and electrolyte homeostasis. Additionally, the kidney has a gluconeogenesis function and also produces hormones and enzymes.
Urine comprises, water, nitrogenous waste, uric acid, electrolytes and other matter. The urinary output rate is typically measured from the bladder. Changes in the urinary output rate may be indicative of one or more conditions including renal failure.
Acute renal failure may be indicative of one or more of the following conditions:                Prerenal failure (hypoperfusion);        Renal failure (intrinsic); and        Postrenal failure (obstructive).        
Prerenal failure is indicative of decreased perfusion without cellular injury, such that the renal tubular and glomerular functions are intact and reversible if the underlying cause is corrected in time.
To date, there are very few reliable methods, if any, for real-time diagnosis of prerenal failure. Thus, all too often, by the time the patient is diagnosed as suffering from prerenal failure, either or both of the kidneys are severely damaged.
Sustained prerenal azotemia is the main factor that predisposes patients to ischemia-induced acute tubular necrosis.
In the case of postrenal failure, it is important to verify if there is any obstruction of the ureters or urethra, since the potential for recovery may be inversely related to the duration of the obstruction.
Renal failure may be classified according to the primary kidney structure suffering the injury, the structure normally being one of tubular, insterstitium, vessel and glomerulus.
To date, renal failure is diagnosed by performing blood tests, urine analysis, by renal indices and physical examination including scans such as ultrasound, Doppler and others However, it should be noted that, for a large part, the blood and urine tests are performed off-line with a delay. This delay is often critical and may significantly reduce the potential for recovery.
Normally, the blood tests and urine tests performed include CBC BUN/creatinine, electrolytes, uric acid, PT/PTT and CK.
An offline test to differentiate between prerenal and renal failure may include checking specific gravity and urinary sodium levels and other parameters. Differences in the values of these parameters may be used to differentiate between these two states.
Nephrotoxins, which have a deleterious effect on the renal perfusion, include, but are not limited to aminoglycosides, NSAIDs and amphotericin.
One of the most troublesome of all problems in critically ill patients is maintenance of adequate body fluid which includes proper balance between fluid input and fluid output. To date, most patients that are hospitalized in the Intensive Care Unit (ICU) are monitored by continuous measurement of several hemodynamic parameters, such as heart rate, invasive blood pressure measurement, central venous pressure (CVP) and occasionally, wedge pressure.
It is well known that one of the most important parameters that reflect proper organ perfusion is the hourly urine output. However, currently the tools and systems that are used are not precise enough. One outcome of this is the high occurrence of acute renal failure (ARF) in ICU's. This complication occurs in a significant percentage of critically ill patients. The most common underlying etiology is acute tubular necrosis, usually precipitated by hypoperfusion and/or nephrotoxic agents. On the other hand, overzealous use of fluid may result in fluid overload, pulmonary edema and, acute respiratory distress syndrome. (ARDS)
The following are explanations of terms and diseases referred to herein.
ARF (Acute Renal Failure)
Acute Renal Failure (ARF) is a syndrome characterized by a rapid decline in the glomerular filtration rate (hours to days), retention of nitrogenous waste products, and perturbation of extracellular fluid volume and electrolyte and acid-base homeostasis. ARF is a complication of approximately 5% of hospital admissions and of up to 30% of admissions to intensive care units. Oliguria (urine output<400 ml_/d) is a frequent but not invariable clinical feature (50%) of ARF. ARF is usually asymptomatic and is diagnosed when biochemical monitoring of hospitalized patients is elevated and may be diagnosed by monitoring hospitalized patients, and is indicated by increases in blood urea and creatinine concentrations. It may complicate a wide range of diseases, which for purposes of diagnosis and management are conveniently divided into three categories:
(1) Diseases that cause renal hypoperfusion without compromising the integrity of renal parenchyma (prerenal ARF, prerenal azotemia) (55%),
(2) Diseases that directly involve renal parenchyma (intrinsic renal ARF, renal azotemia) (40%);
(3) Diseases associated with urinary tract obstruction (postrenal ARF, postrenal azotemia) (5%).
Most incidences of ARF are reversible, the kidney being relatively unique among major organs in its ability to recover from almost complete loss of function. Nevertheless, ARF is associated with high incidence of in-hospital morbidity and mortality rates, in large part due to the serious nature of the illnesses that precipitate the ARF. Severe cases may show clinical or pathologic evidence of acute tubular necrosis (ATN). In contrast, nephropathy classically presents itself as an acute disorder (onset within 24 to 48 hours) but is reversible. GFR (Glomerular Filtration Rate)
The GFR was originally determined by injecting insulin into the plasma. Since inulin is not reabsorbed by the kidney after glomerular filtration, its rate of excretion is directly proportional to the rate of filtration of water and solutes across the glomerular filter. In clinical practice however, creatinine clearance is used to measure GFR. Creatinine is an endogenous molecule, synthesized in the body, which is freely filtered by the glomerulus (but also secreted by the renal tubules in very small amounts). Creatinine clearance is therefore a close approximation of the GFR. The GFR is typically recorded in milliliters per minute (ml/min). Example: A person has a plasma creatinine concentration of 0.01 mg/ml and in 1 hour he excretes 75 mg of creatinine in the urine. The GFR is calculated as M/P (where M is the mass of creatinine excreted per unit time and P is the plasma concentration of creatinine).
Renal failure is the condition in which the kidneys fail to function properly. Physiologically, renal failure is described as a decrease in the glomerular filtration rate. Clinically, this manifests in an elevated serum creatinine. It can broadly be divided into two categories: acute renal failure and chronic renal failure.                Chronic Renal Failure (CRF) develops slowly and gives few symptoms initially. It can be the complication of a large number of kidney diseases, such as IgA nephritis, glomerulonephritis, chronic pyelonephritis and urinary retention. End-stage renal failure (ESRF) is the ultimate consequence, in which case dialysis is generally required until a donor for a renal transplant is found.        Acute Renal Failure (ARF) is, as the name implies, a rapidly progressive loss of renal function, generally characterized by oliguria (decreased urine production, quantified as less than 400 ml per day in adults, less than 0.5 ml_/kg/h in children or less than 0.1 mUkg/h in infants), body water and body fluids disturbance and electrolyte derangement. An underlying cause must be identified to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these underlying causes.        
Acute renal failure can be present concurrently with chronic renal failure. This is called acute-on-chronic renal failure (AoCRF). The acute part of AoCRF may be reversible and the aim of treatment, as in ARF, is to return the patient to their baseline renal function, which is typically measured by serum creatinine. AoCRF, like ARF, can be difficult to distinguish from chronic renal failure, particularly if the patient has not been followed by a physician and no baseline (i.e., past record) blood work is available for comparison.
Before the advancement of modern medicine, renal failure might have been referred to as uremic poisoning. Uremia was the term used to describe the contamination of the blood with urine. Starting around 1847 this term was used to describe reduced urine output, now known as oliguria that was thought to be caused by the urine mixing with the blood instead of being voided through the urethra.
Prerenal Azotemia
Prerenal azotemia is relatively common, especially in hospitalized patients. The kidneys normally filter the blood. When the volume or pressure of blood flow through the kidney drops, blood filtration also drops drastically, and may not occur at all. Waste products remain in the bloodstream and little or no urine is formed, even though the internal structures of the kidney are intact and functional.
Lab tests show that nitrogen-type wastes, such as creatinine and urea, are accumulating in the body (azotemia). These waste products act as poisons when they accumulate, damaging tissues and reducing the ability of organs to function. The build-up of nitrogen waste products and accumulation of excess fluid in the body are responsible for most of the symptoms of prerenal azotemia and acute renal failure.
Prerenal azotemia is the most common form of kidney failure seen in hospitalized patients. Any condition that reduces blood flow to the kidney may cause it, including loss of blood volume, which may occur with dehydration, prolonged vomiting or diarrhea, bleeding, burns, and other conditions that allow fluid to escape circulation.
Conditions in which the volume is not lost, but in which the heart cannot pump enough blood, or the blood is pumped at low volume, also increase the risk of prerenal azotemia. These conditions include shock, such as septic shock, heart failure, and conditions where the blood flow to the kidney is interrupted, such as trauma to the kidney, various surgical procedures, renal artery embolism, and other types of renal artery occlusion.